tbuckley/cabot-search huggingface dataset:
POS0655 HLA-B27 POSITIVITY IN A LARGE MISCEGENATED POPULATION OF 5,389,143 HEALTHY BLOOD MARROW DONORS IN BRAZIL
Authors: G. Resende, P. D. Sampaio-Barros, C. Saad, D. Oliveira, J. S. Bueno Filho, M. Pinheiro
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8-14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil. <h3>Objectives</h3> To estimate the prevalence of HLA-B27 positivity in the Brazilian general population using a large national registry. <h3>Methods</h3> This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives from healthy donors (18-60 years old). Data were analyzed according to race (by self-reported skin color, according the predetermined five terms used by Brazilian Institute of Geography and Statistics [IBGE]), and geographic region of residence. <h3>Results</h3> From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%). There was a difference according to race (Table 1): 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. miscigenated between blacks and whites); 3.95% in Amarelos (Yellows i.e. Asian Brazilians, predominantly of Japanese descent); and 3.18% in Indigenous, p&lt;0.0001. There was also a difference regarding geographic region as shown in Figure 1 (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South, p&lt;0.0001). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population. <h3>Conclusion</h3> Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%, with differences between races, similar to previously published in another miscegenated population <sup>[1]</sup>. There is a positivity gradient from North/Northeast (Pardos/Brown predominant population) to South (White predominant population), suggesting that the genetic background related colonization and internal migratory flows, could explain our findings. <h3>Reference</h3> [1]- Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407-11. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0769 VISCERAL ADIPOSE TISSUE AND ADIPOKINES/CYTOKINES IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: K. Risum, N. Olarescu, K. Godang, H. Marstein, J. Bollerslev, H. Sanner
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Increased visceral adipose tissue (VAT) associates with markers for rheumatic inflammatory and cardiovascular diseases, but knowledge is sparse in juvenile idiopathic arthritis (JIA). <h3>Objectives</h3> To compare VAT mass, lipid profile and selected adipokines/cytokines in patients with JIA with matched controls, and to explore the role of VAT in disease associated inflammation and cardiovascular risk. Moreover, to explore the differences in circulating biomarkers between poly- and oligoarticular disease. <h3>Methods</h3> 60 patients with JIA (50 girls) age between 10–16 years were consecutively recruited at Oslo University Hospital and 60 age-and sex-matched controls were randomly drawn from the National Registry. The JIA group included 30 patients with persistent oligoarticular JIA (oligo disease) and 30 patients with extended oligoarticular or polyarticular disease RF +/- (poly disease). VAT (g) was estimated by dual-energy x-ray absorptiometry. Lipid profile, CRP and adipokines/cytokines (by ELISA) were analyzed. Differences between groups were tested with parametric or non-parametric analyses as appropriate and associations with univariate and multiple linear regression analyses. <h3>Results</h3> VAT (g) was comparable between patients and controls [median (25<sup>th</sup> – 75<sup>th</sup> percentile) 64 (23-149) vs 66 (30-99), p=0.98] and between patients with oligo disease and poly disease [46 (22-123) vs 80 (23-167), p=0.32]. Patients presented lower serum levels of APOA1 and RBP4, and elevated serum levels of IL-6, progranulin and MCP-1 (Table 1) as compared to the controls. Patients with poly disease had lower plasma levels of LDL-C, LILA, IL-1RA, progranulin and VEGF, and elevated serum levels of IL-1b and IL-1b/IL-1RA ratio (Table 1) as compared to patients with oligo disease. No statistically significant differences were seen between neither patients and controls nor patients with oligo disease and poly disease for TC, HDL-C, APOB, CRP, leptin, adiponectin, NGAL, angpl4, angiopoietin, chemerin and resistin. In patients, higher IL-6 [unstandardized B (95% CI) 48.7 (25.1, 72.2), p&lt;0.001], resistin [8.5 (5.1, 11.8), p&lt;0.001] and leptin [2.5 (0.9, 4.0), p=0.002] were identified as correlates for higher VAT. In controls, only higher leptin [unstandardized B (95% CI) 5.3 (3.7, 6.9), p&lt;0.001] was identified as correlate for higher VAT. <h3>Conclusion</h3> Despite similar mass, VAT seems to be closely related to IL-6 and resistin suggesting an active metabolic role in JIA. In addition to IL-6, several pro-inflammatory adipokines/cytokines were increased in JIA potentially playing a role in disease activity. Novel biomarkes, among them IL-1b/IL-1RA system, were identified for differentiating between oligo vs poly disease. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0628 BARICITINIB AMELIORATES BLEOMYCIN-INDUCED PULMONARY AND SKIN FIBROSIS VIA JAK 1/2 INHIBITON
Authors: S. Gulle, A. Çelik, B. Lebe, Ç. Ulukuş, M. Bariş, D. Harmanci, M. Birlik, O. Yilmaz
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (AT-II) and is thought to contribute to fibrosis in lung tissue. Significant JAK/STAT activation was demonstrated in fibroblasts, skin biopsies and scleroderma animal models of patients with Systemic Sclerosis (SSc) [1]. <h3>Objectives</h3> The aim of this study was to determine whether inhibition of JAK2/STAT3 in the experimental model of scleroderma is a potential therapeutic strategy for this disease and to investigate the effects of the JAK 1-2 inhibitor Baricitinib (BAR) on the experimental model of dermal and pulmonary fibrosis. <h3>Methods</h3> Thirty-two healthy 6-8 weeks old female C57BL mice with an average weight of 22±3 grams were included in our study. Before the treatment (baseline), day 15 and day 30 (day 30) the same back area was shaved in all mice and skin thickness was measured under the guidance of skin Ultrasound Biomicroscopy (US). US measurements were chosen to be at least &gt;1 cm from the injection area. Whole lung Computed Tomography (CT) scans of each animal were acquired at post-treatment (day 30). H&amp;E and Masson's Trichrome staining were performed to evaluate skin thickness, pulmonary alveolitis, and fibrosis. The Ashcroft score was assessed on Sirius Red stained lung sections post-treatment. For the molecular evaluation of tissue fibrosis, collagen and α-SMA levels were measured in skin and lung tissues by qRTPCR. <h3>Results</h3> We found that BAR resulted in favorable therapeutic outcomes by affecting the inflammation infiltration and collagen deposition both lung and skin tissues. Immunohistochemical results showed that BAR downregulated the levels of COL1A1 and COL1A2.Treatment with JAK 1-2 selective BAR has been shown to ameliorate BLM-induced skin and lung fibrosis at radiological, pathological and molecular measurements. <h3>Conclusion</h3> As a result of our study, the effect of JAK1-2 selective inhibitor baricitinib treatment on reducing skin and lung fibrosis in a mouse model created with BLM was demonstrated with radiological and pathological examinations. We conclude that JAKinh treatments will be an important research area for the treatment of SSc and other fibrotic diseases in the future. <h3>Reference</h3> [1]Wang W, et al. The JAK/STAT pathway is activated in systemic sclerosis and is effectively targeted by tofacitinib. J Scleroderma Relat Disord. 2020;5(1):40–50. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0839 THE COMPARISON OF MALIGNANCY RISK BETWEEN JAK INHIBITORS AND TNF INHIBITORS IN MULTI-CENTER COHORT STUDY
Authors: T. Uchida, N. Iwamoto, S. Fukui, S. Morimoto, T. Aramaki, F. Shomura, K. Aratake, K. Eguchi, Y. Ueki, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ytterberg et al. demonstrated the concern about the incidence of malignancy during treatment with tofacitinib [1]. However, there is few published data of such adverse events in clinical settings. <h3>Objectives</h3> We aimed to compare the incidence of malignancies in RA patients treated with JAK inhibitors and TNF inhibitors in real-world settings. <h3>Methods</h3> We enrolled 499 RA patients treated with JAK inhibitors (tofacitinib, n=192 or baricitinib, n=104) or TNF inhibitors (adalimumab, n=88 or etanercept, n=115). The standardized incidence ratio (SIR) of malignancies were determined using the general Japanese population. After adjusting the clinical characteristic imbalance by propensity score weighting, we compared the risk of malignancy between JAK inhibitors and TNF inhibitors using Cox proportional hazard models. <h3>Results</h3> Observational period was 961.9 patient-years (PY), and median observational period was 1.3 years. We identified 11 cases (3.7%) of malignancies in JAK inhibitors and 4 cases (2.0%) in TNF inhibitors. The SIR for overall malignancies in TNF inhibitors was comparable with general population (0.94, 95%CI: 0.26–2.41), and the SIR in JAK inhibitors was higher than the general population but no significant difference (1.61/100PY, 95%CI: 0.80-2.88). The adjusted hazard ratio was 0.38 (95%CI: 0.09-1.55) between JAK inhibitors and TNF inhibitors in the risk of malignancies (Figure 1). <h3>Conclusion</h3> We demonstrated that the incidence of malignancy in JAK inhibitors was numerically high but not significant compared with general population and TNF inhibitors. <h3>Reference</h3> [1]Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022; 386: 316-26. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0820 SEX-EQTL ANALYSIS REVEALS A SIGNIFICANT SEX-BIAS IN THE EFFECTS OF SJÖGREN’S SYNDROME ASSOCIATED ALLELES ON GENE TRANSCRIPTION
Authors: G. E. Thorlacius, A. Björk, M. Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Primary Sjögren's syndrome is a systemic autoimmune disease that affects exocrine glands, particularly the salivary- and lacrimal glands, leading to the hallmark symptoms of mucosal dryness. Patients commonly also experience fatigue, joint and muscle pain. Sjögren's syndrome predominantly affects women, with a female-to-male ratio of 14:1. Genetic risk factors associated with Sjögren's syndrome have been identified, however, the mechanisms behind the profound sex-bias remain incompletely understood. <h3>Objectives</h3> The aim of this study was to analyze whether the sex of a carrier of genetic variants associated with Sjögren's syndrome affects the expression of genes in associated loci. <h3>Methods</h3> Genetically regulated gene expression differences between sexes were identified by identifying expression quantitative trait loci (eQTLs). Databases including the Genotype-Tissue Expression project (GTEx, version 8), and the NHGRI-EBI Catalog of human genome-wide association studies (GWAS catalog) as well as a literature review were utilized to extract information about variants significantly associated with Sjögren's syndrome, and their sex-specific eQTL effects. <h3>Results</h3> Out of 22 non-<i>HLA</i> loci identified as associated with Sjögren's syndrome at the genome-wide level, 4 independent loci had one or more significant sex-eQTL effects in the GTEx database in any tissue. These included variants near <i>IRF5</i>, <i>TNIP1</i>, <i>SYNGR1</i> and the <i>BLK-FAM167A</i> loci. Additionally, variants in 4 Sjögren's syndrome associated loci within the <i>HLA</i> region on chromosome 6 were found to have one or more sex-eQTL effects in the GTEx database. Of the 14 identified sex-eQTLs for Sjögren's associated loci, 10 were female biased. <h3>Conclusion</h3> Sjögren's syndrome is a female biased disease and genetic variants associated with Sjögren's syndrome have discordant effects on gene expression in females compared to males. A majority of the identified effects point towards a more severe effect of these variants in female carriers than male carriers, indicating that females could be more profoundly affected by these genetic risk factors than males. This suggests a mechanism where genetic risk factors could disproportionately increase disease risk in one sex compared to the other. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Gudny Ella Thorlacius: None declared, Albin Björk: None declared, Marie Wahren-Herlenius Grant/research support from: Janssen Pharmaceutica NV and Merck KGaA.
POS0427 PROSTAGLANDIN E2 CONTROLS THE METABOLIC ADAPTATION OF T CELLS TO THE INTESTINAL MICROENVIRONMENT
Authors: M. Villa
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immune cells must adapt to different environments during the course of an immune response, such as during their transition from lymph nodes to peripheral tissues. <h3>Objectives</h3> We studied the adaptation of CD8<sup>+</sup> T cells to the intestinal microenvironment and how this process shapes their residency in the gut. Investigation of this process will lead to the identification of tissue-specific mechanisms to target CD8<sup>+</sup> T cell function in a gut-restricted manner. <h3>Methods</h3> We explored the adaptation of CD8<sup>+</sup> T cells to the intestinal microenvironment using single cell RNA and antibody sequencing, mass spectrometry-based metabolomic approaches, CRISPR-Cas9 gene editing, and in vivo mouse models of intestinal infection. <h3>Results</h3> CD8<sup>+</sup> T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate expression of mitochondrial genes. Human and mouse gut-resident CD8<sup>+</sup> T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain their function. We found that the intestinal microenvironment is rich in prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), which drives mitochondrial depolarization in CD8<sup>+</sup> T cells. Consequently, these cells engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS) that result from mitochondrial depolarization. Impairing PGE<sub>2</sub> sensing promotes CD8<sup>+</sup> T cell accumulation in the gut, while tampering with autophagy and glutathione negatively impacts the T cell population. <h3>Conclusion</h3> A PGE<sub>2</sub>-autophagy-glutathione axis defines the metabolic adaptation of CD8<sup>+</sup> T cells to the intestinal microenvironment, to ultimately influence the T cell pool. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0756 EFFICACY AND SAFETY OF ADALIMUMAB IN PEDIATRIC NON-INFECTIOUS NON-ANTERIOR UVEITIS: REAL-LIFE EXPERIENCE FROM AIDA INTERNATIONAL REGISTRY
Authors: C. Fabiani, A. Vitale, F. Della Casa, S. Guerriero, G. Ragab, A. Brucato, M. Cattalini, E. Del Giudice, A. Marino, M. P. Paroli, C. Gaggiano, J. Sota, V. Caggiano, M. Tarsia, B. Frediani, L. Cantarini
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Evidence about the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious intermediate uveitis/pars planitis, posterior uveitis and panuveitis is still limited. <h3>Objectives</h3> Aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. <h3>Methods</h3> This is an international multicenter study based on real-life data from pediatric patients treated with ADA due to non-anterior uveitis. Data were drawn from the retrospective branch of the AutoInflammatory Disease Alliance (AIDA) registry dedicated to uveitis. Figure 1 provides the flow diagram describing the selection of the patients enrolled on October 1st, 2022. <h3>Results</h3> 21 patients (36 affected eyes) were enrolled. Eleven patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a partial response with reduced frequency of relapses (3 cases), reduced severity of relapses (3 cases) or reduced frequency and severity of relapses (4 cases). The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (<i>p</i>=0.0009). Macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoids dosage significantly decreased at the last assessment (<i>p</i>=0.005). As observed in Table 1, intermediate uveitis/pars planitis (<i>p</i>=0.01) and posterior uveitis (<i>p</i>=0.03) were more frequent among patients with full response to ADA; panuveitis was significantly more frequent among patients continuing to experience uveitic flares (<i>p</i>=0.001). Regarding the safety profile, a case of generalized adenopathy was observed. <h3>Conclusion</h3> ADA had a role in all pediatric patients with non-anterior uveitis with a significant glucocorticoid sparing effect. Panuveitis seems to be more frequent among patients continuing to experience uveitic flares. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0419 THE ROLE OF OROSOMUCOID 2 IN THE REGULATION OF BONE REMODELING BY INHIBITING OSTEOCLASTOGENESIS AND PROMOTING OSTEOGENESIS
Authors: M. S. Lee, C. H. Chung, W. H. Yoo, Y. Choi, C. H. Lee
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Orosomucoid (ORM) is one of the acute phase reactant protein family and is expressed in hepatocytes and secreted into plasma under stress conditions such as tissue injury, infection, and inflammation. Three types of ORM are known to date (ORM1, 2 and 3), and ORM2 is mainly expressed in bone marrow cells. ORM2 has only some studies on hepatic metabolism, inflammation and immune regulation, and no studies on bone metabolism have been reported. <h3>Objectives</h3> The aim of this study is to reveal the role of ORM2 in the differentiation and function of osteoclasts and osteoblasts. <h3>Methods</h3> To determine the effect of ORM2 on RANKL-induced osteoclast differentiation and function, we performed TRAP staining, F-actin stating, and bone resorbing assay using ORM2 recombinant protein or ORM2 siRNA. Also, the effect of ORM2 on osteogenesis was confirmed by ALP and ARS assay. The intracellular mechanisms responsible for the dual regulation of osteoclastogenesis and osteogenesis of ORM2 were revealed by western blotting and quantitative real-time RT-PCR. <h3>Results</h3> We found that ORM2 is a potential target for osteoporosis therapeutics, as treatment with this agent enhances osteoblast differentiation and bone growth and suppresses osteoclast differentiation and bone resorption by performing gain- and loss-of-function studies. During ORM2-mediated regulation of osteoclastogenesis, phosphorylation of early signal transducers such as p38, JNK, Akt, IκB, PLCγ2, and Btk was affected, which in turn altered the mRNA and protein levels of c-Fos and NFATc1. ORM2 also increased ALP, Alizarin Red-mineralization activity, and the expression of osteoblastogenic gene markers, such as Runx2, osteocalcin (OCN), and ALP in mouse calvarial primary osteoblasts, and activated the p38-Runx2 pathway, which enhanced osteoblast differentiation. <h3>Conclusion</h3> we suggest that ORM2 may be a promising candidate for gene therapy for bone metabolic diseases, and further serve as a potentially important biomarker in the field of bone disease diagnosis. <h3>References</h3> [1]Hochepied T, Berger FG, Baumann H, Libert C. Alpha (1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev. 2003;14(1):25-34. [2]Fagerberg L, Hallström BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13(2):397-406. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0770 CAREGIVER BURDEN IN INDIAN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS: A SINGLE HOSPITAL-BASED STUDY
Authors: N. Gowda, A. Balakrishnan, A. Lawrence, A. Aggarwal
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Caring for a child with juvenile idiopathic arthritis (JIA) negatively impacts caregivers. There are no studies on caregiver burden in JIA from South Asia. <h3>Objectives</h3> To assess the caregiver burden in children with JIA from India. <h3>Methods</h3> We conducted this observational study in a Tertiary care center in North India. We translated and culturally adapted the CAREGIVER QUESTIONNAIRE<sup>[1]</sup> into Hindi and administered it to 145 caregivers of JIA patients age ≤ 18 years from November 2021 to December 2022. We collected their socio-economic data, clinically examined the child and reviewed their clinic records for disease characteristics including activity and damage. The Juvenile Arthritis Multidimensional Assessment Report was used to assess the physical function and health related quality of life. The CAREGIVER QUESTIONNAIRE was scored<sup>[2]</sup> to determine impact in various domains. <h3>Results</h3> One hundred and forty-five caregivers participated with median age of 39 (32-45) years. This included 68 (47.9%) fathers, 34 (23.4%) mothers, 22 (15.2%) brothers, 18 (12.4 %) uncles and 1 (0.7%) sister, grandfather and grandmother. The JIA patients had median age of 15 (12-17) years and the male: female ratio 2.4:1. Enthesitis related arthritis was the predominant subtype (65.5%) followed by systemic onset JIA (11.7%), RF+ polyarthritis (9.0%), RF- polyarthritis (6.9%), oligoarticular JIA (6.2%) and extended oligoarticular (0.7%). Majority (69.7%) expressed sadness at diagnosis, and one fourth (28.3%) continued to express sadness. Half (53.4%) of the caregivers neglected their health and one tenth (9.7%) became sick. Two thirds (64.8%) had to borrow money to meet the expenses. Emotional impact scored 12.9 ± 2.3 (range 4-18). Social impact scored 6.1 ± 1.9 (range 2-9), economic impact 2.6 ± 1.0 (range 0-5), labour impact 7.0 ± 4.2 (range 0-15), family impact 6.8 ± 1.6 (range 4-16) relationship impact 0.6 ± 0.5 (range 0-0.8). Impact on spirituality was 0.9 ± 0.6 (range 0-5) and impact of social networks was 0.8 ± 0.8 (min= 0, max=8). Total score was 37.8 ± 9.2 (range 10-84). <h3>Conclusion</h3> JIA has significant emotional, social, economic and labor impact on caregivers. Social support needs to be given to caregivers for caring for children with JIA. <h3>References</h3> [1]Torres-Made MD, et. al. Development and validation of the CAREGIVERS questionnaire: multi-assessing the impact of juvenile idiopathic arthritis on caregivers. Pediatr Rheumatol Online J. 2020 Jan 14;18(1):3. [2]Fortuna-Reyna BJ, et. al. Psychosocial and economic impact of rheumatic diseases on caregivers of Mexican children. Pediatr Rheumatol Online J. 2021 Mar 17;19(1):30. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.